Diabetes in Pregnancy a Risk Factor for CVD

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A history of gestational diabetes appears to be associated with early atherosclerosis as measured by common carotid intima media thickness.

The association was independent of pre-pregnancy obesity among women who have not developed type 2 diabetes or metabolic syndrome.

A history of gestational diabetes may be a marker for early atherosclerosis, even in women who were not obese before pregnancy and have not gone on to develop diabetes or metabolic syndrome after giving birth, researchers reported.

In 777 women without a diagnosis of diabetes or metabolic syndrome after pregnancy, mean carotid intima media thickness (ccIMT) was 0.023 mm higher in women who had developed gestational diabetes than in those who had not, after controlling for race, age, parity, and pre-pregnancy body mass index (0.784 versus 0.761, P=0.039), wrote Erica P. Gunderson, PhD, MS, MPH of Kaiser Permanente and her co-authors online in the Journal of the American Heart Association.

Carotid intima media thickness is a subclinical measure of early atherosclerosis that "strongly predicts" heart disease and stroke, especially in women, the authors noted.

The study also found that weight gain and increase in blood pressure seemed to mediate thickening of the IMT. "Managing weight gain and blood pressure would be something important in preventing heart disease in women with a history of [gestational diabetes]," Gunderson told MedPage Today.

Studies have reported a 66% to 85% higher risk of CVD, including coronary artery disease, myocardial infarction, or stroke, as well as 56% higher risk of self-reported CVD in women who have had gestational diabetes, the authors said.

"It has been unclear, however, whether gestational diabetes increased risk of early atherosclerosis independent of pre-pregnancy obesity and subsequent metabolic disease," the investigators said.

The lack of clarity stems from the fact that the earlier findings were based on administrative or clinical databases with retrospective or cross-sectional study designs, the authors wrote. Such studies, they said, have limited ability to distinguish whether gestational diabetes and CVD association is due to pre-pregnancy obesity, the gestational diabetes pregnancy, or the future onset of diabetes or metabolic syndrome.

"Longitudinal designs with frequent metabolic screening during the reproductive years (before and after pregnancies) are essential to the evaluation of a history of gestational diabetes as an independent risk factor for early atherosclerosis prior to the onset of metabolic diseases," the authors said.

The study included 898 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a biracial, population-based, multicenter, longitudinal, observational study. Of those, 119 (13%) reported a history of gestational diabetes (7.6 per 100 deliveries).

All of the women were free of diabetes and heart disease at baseline in 1985-1986, had delivered at least one child after baseline, and had common carotid intima media thickness measured in 2005-2006, at an average age of 44. Follow-up exams occurred at 7, 10, 15 and 20 years.

The findings of this study, the authors said, challenge the assumption that CVD risk is solely the result of higher risk of diabetes and metabolic syndrome after pregnancy in women who had gestational diabetes.

This is particularly important, the authors said, because the majority of women with a history of gestational diabetes, while they may have persistent mild to moderate insulin resistance and dyslipidemia, do not develop overt diabetes in midlife.

In 2011, the American Heart Association's Recommendations for Prevention of Heart Disease in Women added pregnancy complications such as gestational diabetes and preeclampsia to the recommendations for risk assessment for prevention of heart disease. However, with regard to gestational diabetes, that risk was based on the elevated risk for diabetes and metabolic syndrome.

The American Diabetes Association and the American College of Obstetrics and Gynecology also both recommend early postpartum screening for diabetes after a gestational diabetes pregnancy, and repeat screenings annually for women with impaired glucose values, the authors said.

"But impaired glucose values are only one risk factor for heart disease," Gunderson told MedPage Today. Other risk factors for heart disease that should be monitored in these women include blood pressure and lipid levels, she said.

This research adds to a growing body of literature that suggests that pregnancy, which is a stress on a woman's system, can reveal underlying predispositions for the development of chronic diseases in mid-to-late life.

One limitation of the study, the authors noted, was the lack of IMT measurement before or during pregnancy, which might have ascertained whether higher IMT preceded the onset of gestational diabetes.

The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts from the National Heart, Lung and Blood Institute (NHLBI), the Intramural Research Program of the National Institute on Aging (NIA), and an intra-agency agreement between NIA and NHLBI. The analyses were supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases and the Kaiser Permanente of Northern California Community Benefit Program.

The authors did not disclose any relevant relationships with industry.

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania